Dissecting The Pseudoexfoliation Syndrome With Complementary Genetic, Proteomic And Biophysical Strategies
Funder
National Health and Medical Research Council
Funding Amount
$490,352.00
Summary
Pseudoexfoliation syndrome (PEX) is an eye condition in which flaky material deposits in the eye, greatly increasing the risk of cataract and glaucoma which can lead to blindness. PEX is also associated with heart disease, strokes and aneurysms. Cataract surgery in PEX patients has a higher rate of complications. In this project we will determine the nature of PEX material and why it forms. This knowlege will facilitate better diagnosis and treatment of PEX preventing associated blindness.
Translating Genetic Determinants Of Glaucoma Into Better Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$9,466,000.00
Summary
Glaucoma is the leading cause of irreversible blindness worldwide. By 2020, it will affect 80 million people, and in Australia over the next decade, the overall cost of glaucoma will reach $4.3 billion per annum. This Program will use genetic advances to personalise treatment. Blindness will be prevented in individuals at highest risk, new ways to treat patients will be developed, and better outcomes for patients will result from less treatment and monitoring of low risk cases.
Most eye diseases have a genetic contribution, whether rare disorders affecting children such as retinoblastoma or congenital cataracts through to common disorders of older people such as myopia, age-related macular degeneration or glaucoma. We will continue our successful research to find genes that cause these diseases and use this to improve patient care and prevent blindness. We will work out how families can use this genetic information to participate in trials to develop new treatments.
Young Adult Myopia: Genetic And Environmental Associations
Funder
National Health and Medical Research Council
Funding Amount
$809,271.00
Summary
Myopia affects 80% of school leavers in the cities of East Asia, 45% of Asian Australian school leavers and is probably on the rise in European Australian adolescents. Increased levels of education and lack of time outdoors are known to increase the risk of myopia. We will examine 2,000 young adults to find the genes that interact with these risk factors. In addition to confirming when these risk factors are most important, identifying molecular pathways opens the avenue of new treatments.
Strabismus is the pathological misalignment of the eyes associated with loss of binocular vision and is one of the most common human ophthalmological disorders. Patients with comitant strabismus have full eye movements, whereas patients with incomitant strabismus have limited eye movements, which causes the angle of strabismus to vary with gaze direction. This project aims to define genetic contributors to comitant congenital strabismus.
AusDiab 3: Emerging Risk Factors For And Long-term Incidence Of Cardio-metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$2,616,397.00
Summary
This study will track 11,000 Australian adults over 12 years to determine how many develop diabetes, obesity, kidney and heart disease. The study will develop ways to best predict those who are going to develop these conditions before they have arisen, and will explore a range of novel risk factors to better understand these conditions.
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
A Genome-wide Search For Genes Underlying The Developmental Origins Of Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,022,552.00
Summary
Epidemic rises in the incidence of many chronic diseases such as obesity, type 2 diabetes, hypertension, coronary artery disease and mental illness have occurred in Australia over the last two decades. Antenatal, early life and childhood factors have been consistently associated with the development of such diseases. We propose to conduct a genome-wide scan in an exceptional longitudinal birth cohort in order to identify the genetic mechanisms linking early life event and adult disease.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$285,990.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin i ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin is down-regulated by either erythroid differentiation or the haem precursor protoporphyrin IX (Becker and Richardson, submitted). These data strongly suggest a role for frataxin in iron metabolism. In the present study we will continue to assess if frataxin plays a role in the way cells handle iron. Using a unique model of mitochondrial iron overload developed in my lab (Richardson et al. (1996) BLOOD 87:3477), we will extensively investigate the iron metabolism of the mitochondrion in order to determine the function of frataxin and its role in Friedreich's ataxia. In addition, we have developed a series of new drugs known as iron chelators that can enter the mitochondrion due to their high lipid solubility (Becker and Richardson 1999 J. Lab. Clin. Med. 134:510). These latter drugs are far more effective than the chelator currently used to treat iron overload, desferrioxamine (DFO). Indeed, our chelators have been designed to result in high iron chelation efficacy but low toxicity (see Becker and Richardson, 1999). This exciting research may be crucial in understanding the development of FA and in creating new therapies such as the use of iron chelators.Read moreRead less